Development of predictive biomarkers to stratify potential best-responsive cancer patient populations and to predict the early treatment response to a novel IL-2/IL-15Rbg agonist, RLI, in oncology (MM, RCC, NSCLC, oral). – SELECTIMMUNONCO

This academic/industry collaborative partnership should contribute towards the goals of the challenge «health & wellness» (axis: Translational research in Healthcare). Cancer is the 2nd cause of mortality in France and worldwide.
SELECTIMMUNONCO aims at characterizing and comparing the different immune contextures of 4 types of human metastatic cancers (melanoma, kidney, lung and oral) by decoding these last ones at the primary and metastatic levels and in blood and by making correlations with the mutational status of such tumors. The ultimate goal is to identify relevant biomarkers and signatures which could be helpful and guide the clinical development of novel IL-2/IL-15Rbg agonists like the super IL-15, RLI-15. RLI-15 has been developed over the last five years by our teams and will enter clinical trials within 18 months (GMP biomanufacturing is underway). Finally, therapeutic success will also depend on the elucidation of the entire network of immune signalling pathways that regulate immune responses in the tumour microenvironment. These regulatory mechanisms are probably influenced by the specific type of cancer, which has its own unique set of genetic, epigenetic and inflammatory changes that evolve with the advancement of disease. Understanding these networks will provide new targets for modulation and, ultimately, will result in improved combinatorial immunotherapies for the successful treatment of cancers. We need to know more about which mechanisms are relevant in which types of human cancers and especially in which detailed subpopulations of patients, and when and where several mechanisms operate simultaneously. We also need to find reliable tools as signatures, biomarkers and matrices to check their swinging activity in patients’ tumors, and develop appropriate therapeutic interventions to restore effective antitumor mechanisms.
The development of such analytical matrices of the antitumor immune responses within a specific tumor indication and inter-tumor indication, of such functional immune matrices through the pharmacological stimulation of TILs with RLI-15 with or without anti-PD1 agents should allow us to better stratify potential best-responsive patient populations to a treatment using RLI-15 and to spare potential non-responders. In addition, appropriate predictive markers of response to such treatments will be developed to optimize the care of the patients. Last, extrapolating and applying such stratification matrices to in vivo experimental tumor models would permit to better define optimal drug combinations and sequences with RLI-15.

To conclude, SELECTIMMUNONCO aims at improving the response rates and duration of response to a treatment using IL-2/IL-15Rbg agonists like RLI-15, in potential best-responsive patient populations thanks to appropriate stratification of patients with cancers which are already known to partially respond to IL-2 and anti-PD1 therapies.